Could the MDR-1 gene & seizures be connected?

I just had one of those ‘ah-ha’ moments as I was reading through one of the many neonatal puppy pages I’ve been devouring all weekend. Someone was posting about MDR-1 sensitivity in dogs (worrying about giving Ivermectin to their puppies).

I don’t know why but I have never actually questioned what ‘MDR’ stands for. But the author of that discussion wrote it out in full: ‘Multi-Drug-Resistance’.

Reading this kicked my brain into hyper-analytical mode (this happens to me often; you’ll get used to it if you stick around long enough). And the conclusion I landed at knocked the wind out of me:

Could the MDR-1 gene be at the root of the seizure disorders we see in so many border collies?

Let me explain my thinking…

First, MDR-1 positive dogs are prone to severe and even lethal reactions to Ivermectin, a commonly used deworming drugs. According to this article, they are also sensitive to many other medications, hence the name ‘multi-drug-resistance’, including (but not limited to) the following:

Abamectin

Acepromazine

Actinomycin D

Aldosterone

Amitriptyline

Butorphanol

Cortisol

Cyclosporine

Dexamethasone

Digoxin

Diltiazem

Docetaxel

Domperidone

Ketoconazole

Doxorubicin

Doxycycline

Erythromycin

Etoposide

Itraconazole

Ivermectin(antiparasitic)

Levofloxacin

Loperamide(Immodium)

Methylprednisolone

Milbemycin(Trifexis)

Morphine

Moxidectin

Ondansetron

Paclitaxel

Selamectin

Sparfloxacin

Tacrolimus

Talinolol

Terfendadine

Tetracycline

Vecuronium

Verapamil

Vinblastine

Vincristine

This same article stated that up to 50% of Aussie Shepherds are MDR-1 positive. Border collies and other herding breeds are equally prone.

Very crudely, MDR-1 positive dogs have a gene mutation that prevents the body from clearing various drugs out of the brain. As a result, the drug build up can cause neurological disorders, including seizures (and ataxia and death, among other things).

Basically, (as I understand it from the brief research I have done to date), drugs build up in the brain, the dog can’t clear them out, and the brain & nervous system shorts out.

Now… connecting this to seizures: Scientists have been searching for an epilepsy gene in dogs for years, and there does seem to be some family inheritance pattern for some cases. Recently they have found such a gene in some breeds.

In cases of classic idiopathic epilepsy, dogs typically develop seizures that are then controlled with anti-convulsant drugs. These dogs often go on to live a long, happy life.

But others develop seizures that increase in intensity, often getting worse with time, leading to a need to euthanize. These dogs are commonly assumed to have had some kind of tumour that grew rapidly, causing the increase in seizures and eventual death.

That may be so in some cases, but what if the dog that fit this latter description was in fact drug sensitive? What if the reason his seizures got worse was because the anti-convulsant drugs he was given backfired by building up in his brain? What if each dose made him a bit more toxic, instead of helping stabilize him?

What if the seizures started as a drug reaction in the first place? Just the one extra vaccine, or dose of flea and tick medication, that put the level of brain toxicity over the limit?

What if such dogs have some mutation that prevents their bodies from clearing drugs – be it the MDR1 gene, or some other – but if they were kept drug free would live normal, happy lives?

I wonder if anyone is doing any research along this thinking. It might save an awful lot of heartache and loss. Better yet, what if we stopped administering all these drugs, just to be on the safe side?